Interface apparatus for capillary electrophoresis to a matrix-assisted-laser-desorption-ionization mass spectrometer

Abstract

An apparatus for collecting samples from capillary electrophoresis (CE) for matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) is disclosed. The apparatus has a capillary, a metallic support, a porous member, and a power supply for applying an electrical potential between the porous member and an inlet end of the capillary to drive the sample through the capillary during CE. The capillary transmits a sample from the inlet end to the exit end during capillary electrophoresis. The metallic support supports the porous membrane such that the porous membrane contacts the capillary exit end during CE. The metallic support (with the porous membrane) is suitable for placing in a mass spectrometer to act as a repeller for MALDI. The porous member has at least a portion thereof that is generally concentric with the capillary exit end and contacts the porous membrane during CE. The capillary exit end and the metallic support are adapted to lift the capillary exit end from the porous membrane and reposition it on the porous membrane at a different location to deposit noncontinuously different fractions of the sample exiting the capillary on the porous membrane. When an electrically conducting liquid is present in the porous member, it provides electrical communication between the capillary exit end and the power supply.

What is claimed is: 
     
       1. An apparatus for collecting analyte samples from capillary electrophoresis (CE) for matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS), comprising: (a) capillary, having an inlet end and an exit end, for conducting analyte and fluid during CE;   (b) metallic support for supporting a porous membrane such that the porous membrane can substantially contact the capillary exit end during CE, the metallic support being suitable for placing with the porous membrane in a mass spectrometer to act as a repeller for MALDI;   (c) porous member having at least a portion thereof contacting and being generally concentric with the capillary exit end, the porous member and the capillary exit end being adapted to enable substantially contacting the porous membrane during CE, and being adapted to separate the capillary exit end from the porous membrane for repositioning such that the capillary exit end substantially contacts the porous membrane at a different location to deposit noncontinuously different fractions of the sample, the porous member being capable of conducting electricity in the presence of an electrolyte; and   (d) power supply for applying an electrical potential between the porous member and the inlet end of the capillary to drive analyte through the capillary during capillary electrophoresis when an electrolyte provides electrical communication between the capillary exit end and the porous member.   
     
     
       2. The apparatus according to claim I further comprising the porous membrane, wherein the porous membrane has a surface adapted to hold a MALDI matrix and elution fractions from CE. 
     
     
       3. The apparatus according to claim 2 wherein the matrix is selected from the group consisting of nicotinic acid, 2,5-dihydroxybenzoic acid, sinapinic acid, succinic acid, glycerol, α-cyano-4-hydroxycinnamic acid, and 3-hydroxypicolinic acid. 
     
     
       4. The apparatus according to claim 2 wherein the porous membrane is a hydrophilic polymeric membrane. 
     
     
       5. The apparatus according to claim 4 wherein the hydrophilic polymeric membrane is a polyolefin membrane. 
     
     
       6. The apparatus according to claim 4 wherein the hydrophilic polymeric membrane is made of polypropylene or polyethylene. 
     
     
       7. The apparatus according to claim 1 wherein the porous member and the capillary exit end both substantially contact a common surface of the porous membrane during capillary electrophoresis. 
     
     
       8. The apparatus according to claim 1 further comprising a reservoir in fluid communication with the porous member to supply the electrolyte thereto. 
     
     
       9. The apparatus according to claim 1 wherein the metallic support is a metallic plate. 
     
     
       10. A method for interfacing capillary electrophoresis (CE) and matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) for analysis of a sample suspected of containing analyte, comprising: substantially contacting a porous membrane with a porous member and with an exit end of a capillary to provide fluid communication via an electrolyte such that during CE an electrical potential can be implemented between an inlet end of the capillary and the porous member to deposit fractions of the sample noncontinuously on different areas of the porous membrane by lifting the capillary exit end and the porous member from the porous membrane and repositioning on the porous membrane at a different location to deposit different fractions of the sample exiting the capillary, at least a portion of the porous member is generally concentric with the capillary exit end, such that the porous membrane with the fractions deposited thereon can be processed and placed in a mass spectrometer for MALDI to analyze the sample.   
     
     
       11. The method according to claim 10 further comprising supporting the porous membrane during CE with a metallic support such that the porous membrane and the metallic support can be put in a mass spectrometer for MALDI so that the metallic support will act as a repeller. 
     
     
       12. The method according to claim 11 wherein the MALDI matrix further comprising: placing the porous membrane and the metallic support in a mass spectrometer, such that the metallic support acts as a repeller for MALDI in MS. 
     
     
       13. The method according to claim 10 wherein a MALDI matrix is applied on the fractions after the fractions are deposited on the porous membrane. 
     
     
       14. The method according to claim 10 wherein the capillary exit end is inserted through the porous member. 
     
     
       15. The method according to claim 10 wherein a matrix selected from the group consisting of nicotinic acid, 2,5-dihydroxybenzoic acid, sinapinic acid, succinic acid, glycerol, α-cyano-4-hydroxycinnamic acid, and 3-hydroxypicolinic acid is deposited on the porous membrane. 
     
     
       16. The method according to claim 10 wherein a hydrophilic polymeric membrane is used for the porous membrane. 
     
     
       17. The method according to claim 10 wherein a hydrophilic polypropylene or polyethylene porous membrane is used for the porous membrane. 
     
     
       18. A method for interfacing capillary electrophoresis (CE) and matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS), comprising: positioning a porous member and an exit end of a capillary for CE proximate thereto noncontinuously on a porous membrane supported with a metallic support such that at least a portion of the porous member is generally concentric with the exit end of the capillary, the porous member and the capillary exit end substantially contacting the porous membrane noncontinuously while eluting the sample during CE through the capillary, the elution being effected by contacting the capillary exit end and the porous member with an electrolyte and implementing an electrical potential between an inlet end of the capillary and the porous member, said substantially noncontinuously contact being implemented by lifting the capillary exit end and the porous member from the porous membrane and repositioning on the porous membrane at a different location, thereby depositing fractions of the sample on different areas of the porous membrane such that the porous membrane with CE eluents deposited thereon is suitable for MALDI-MS.   
     
     
       19. A method of making an apparatus for collecting fractions from capillary electrophoresis (CE) for matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS), comprising: (a) inserting a CE capillary that has an inlet end and an exit end into a porous member such that at least a portion thereof is generally concentric to the exit end of the capillary and the exit end is about flush with a surface of said portion of the porous member, for elution of CE analytes during capillary electrophoresis;   (b) positioning a metallic support proximate the exit end of capillary, for supporting a porous membrane such that the porous membrane substantially contacts the capillary exit end during capillary electrophoresis, the metallic support being suitable for placing with the porous membrane in a mass spectrometer to act as a repeller for MALDI, the capillary exit end and the metallic support being adapted to separate the capillary exit end from the porous membrane and reposition on the porous membrane at a different location to deposit noncontinuously different fractions of fluid exiting the capillary on the porous membrane during CE; and   (c) providing a power supply suitable for applying an electrical potential between the porous member and the inlet end of the capillary to drive the CE analytes through the capillary during CE when an electrolyte provides electrical communication between the capillary exit end and the porous member.